Individuals characterized as high novelty seekers are more likely to abuse alcohol and other drugs, relapse, and fail to comply with treatment for alcohol and drug dependence. Artificial selection for divergent expression of a behavior is an elegant and rapid way to demonstrate the influence of genetic factors on the behavior, as well as to provide a means to examine correlated differences in related behaviors. The current proposal seeks to create lines of mice artificially selected to differ in the expression of a model of novelty reeking, and then to compare these selected mice for the rewarding effects of alcohol, and to determine if these effects generalize to amphetamine. Finally, the role of the dopamine D4 receptor in the expression of novelty seeking will be evaluated using both agonists and antagonists specific to the D4 receptor, as well as the comparison of D4 deficient mice to wild-type mice on several models of novelty seeking. These experiments will provide valuable insights into the genetic association between novelty seeking and drug abuse, and provide a useful model for preclinical evaluation of potential therapeutic agents aimed at reducing dependence.